Abstract 1857: 3p12.3 and 7q36.3 harbor genes associated with hereditary breast and colorectal carcinomas

Abstract

Abstract Lynch syndrome (LS) is the most common hereditary syndrome that predisposes to colorectal cancer (CRC). LS is associated with susceptibility to proximal colon cancer, multiple primary (CRC) and extra-colonic tumors. According to Registration of Hereditary Colorectal Cancer (RHCC) of AC Camargo Hospital of Brazil, breast cancer is the most frequent extra-colonic tumor among women with suspicion of hereditary CRC, suggesting the possibility of a new syndrome known as Hereditary Breast and Colorectal Cancer (HBCC). Array comparative genomic hybridization (array CGH) is the high-resolution laboratory technique of choice for the detection of chromosomal DNA copy number alterations on a genome-wide scale. The aim of the present study was to identify copy number alterations in genes related to predisposition in HBCC syndrome. Array comparative genomic hybridization was performed using Human 4 × 180K Oligoarrays (G4449A, Agilent) in 47 individuals from families showing HBCC phenotype. For each sample, 800 ng of DNA were fragmented by a double enzymatic digestion (AluI + RsaI). DNA from peripheral blood leukocytes and control DNA from Promega (Human Genomic DNA Female G1521) were labeled with CY3-dCTP and CY5-dCTPs, respectively, and hybridized at 65°C for 17 h. The chips were scanned on an Agilent DNA Microarray Scanner and image analysis was done using the Feature-Extraction version 10.1.1.1 software (Agilent Technologies). Raw copy number ratio data were transferred to the Agilent Genomic Workbench Software (version 5.0.14) for further analysis. It was detected copy number variations involving 36 regions previously described in genome databases. Furthermore, it was observed loss at 3p12.3 in two individuals. One patient presented breast cancer and CCR while the other one had breast carcinoma. Both of them had breast cancer around the 50 years. In both families, their relatives had CCR, breast cancer and endometrial cancer, which is another extra-colonic tumor found among patients with LS. In a third women with breast and colorectal carcinomas was detected deletion at 7q36.3. Germline copy number alterations may indicate new genes associated with cancer predisposition. Our results suggest that 3p12.3 and 7q36.3 harbor genes associated with hereditary breast and colorectal carcinomas. Additional members of these families are being evaluated to confirm the involvement of these regions as candidate genes. Financial Support: FAPESP (2008/57887-9) and CNPq (57589/2008-9). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1857.